DESCRIPTION: Transplantation therapy has become standard for high-risk or recurrent NHL and HD. Although conditioning regimens, progenitor cell collection techniques, and patient selection criteria differ, for most patients the primary hazard is post-transplant malignant relapse. The investigators have previously reported peri-transplant immune-stimulating cytokine therapy using IL-1alpha, IL-2 and autologous activated NK (ANK) cell infusions. They are now proposing a series of clinical and related preclinical investigations to minimize the peri-transplant tumor burden and to reduce the risk of post-transplant recurrence. Toward the goal this application has three specific aims. Specific Aim 1 will clinically evaluate IL-2 based post-transplant immunotherapy using extended daily subcutaneous IL-2 combined with ex vivo IL-2 activated autologous ANK infusions. The feasibility, tolerance and anti-tumor efficacy of IL-2/ANK therapy will be determined using prospective clinical observation and studies of lymphoid effector in vitro cytolytic function. Specific Aim 2 will clinically evaluate the safety and potency of daily subcutaneous IL-2 supplemented with intermittent bolus IL-2 as compared to ex vivo activated ANK infusions studied in specific aim 1. In Specific Aim 3 the investigators will initiate a randomized clinical trial of autologous peripheral blood stem cell transplantation for lymphoma and formally test the clinical value of post-transplant IL-2 along with activated ANK or bolus IL-2 as determined by Aims 1 and 2. Through both initial pilot studies and the subsequent randomized trial a prospective assessment of in vivo immune activation will be correlated with protection against post-transplant relapse.